Organofluorine compounds are of significant importance for the agrochemical and pharmaceutical industries as well as for PET imaging applications.[1] Despite the broad impact of organofluorine compounds and the intrinsic strength of the C—F bond, the incorporation of fluorine into organic molecules remains challenging.[1e, 2] Conventional fluorination methods typically involve harsh reaction conditions, displaying poor functional group tolerance and low selectivity.[2b] These limitations have inspired the development of a number of new methods, especially catalytic approaches, for constructing a C—F bond.
The majority of these newly-developed methods are based on electrophilic fluorination reagents (F+), such as Selectfluor and other N-fluoroammonium analogs,[4] N-fluoropyridinium salts (NFPs),[5] and N-fluorosulfonamides.[6]
For catalytic fluorinations with fluoride-based reagents (F−),[3a] only a handful of reactions have been developed for the synthesis of aryl and heteroaryl fluorides,[7] alkenyl fluorides,[8] allylic fluorides,[9] fluorohydrins,[10] 18F-labeled trifluoromethyl aromatics,[11] and benzylic fluorides.[12]
A general catalytic method for constructing aliphatic C—F bonds with simple nucleophilic fluoride remains a challenging task.[13] An efficient aliphatic C—H fluorination reaction that employed manganese tetramesitylporphyrin, Mn(TMP)Cl, as the catalyst and silver fluoride/tetrabutylammonium fluoride trihydrate (TBAF.3H2O) as the fluoride source was reported.[14] The reaction was shown to proceed through a trans-difluoromanganese(IV) porphyrin complex that served as the fluorine transfer agent. Insights gained from the facile capture of substrate carbon radicals by F—Mn(IV)-F species led to the development of benzylic C—H fluorination reactions using manganese salen catalysts.[15] The first 18F labelling reaction of aliphatic C—H bonds with no-carrier-added [18F]fluoride and Mn(salen) catalysts was also reported.[16]